Malignant Hyperthermia Clinical Overview
I. The "On-Call" Snapshot
Clinical Significance in Malaysia: This is a rare but potentially fatal hypermetabolic crisis triggered by common anaesthetic agents in our Operating Theatres. Every doctor, especially those in Anaesthesia, Surgery, and Emergency, must be able to recognise and manage it immediately.
High-Yield Definition: Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anaesthetic agents (like sevoflurane, desflurane, isoflurane) and the depolarizing muscle relaxant succinylcholine.
Clinical One-Liner: Basically, the anaesthetic drugs make the patient's muscles contract uncontrollably, cooking them from the inside out and producing a massive amount of acid.
II. Etiology & Risk Factors
Etiology: It's a genetic condition. An autosomal dominant inherited disorder. The primary defects are in genes that control calcium release in muscle cells.
Ryanodine receptor gene (RYR1): Responsible for >50% of cases.
CACNA1S gene: Less common cause.
Risk Factors:
Non-modifiable:
A known personal or family history of MH (this is the single biggest red flag in your pre-op assessment).
History of unexplained complications during previous anaesthesia (e.g., high fever, dark urine post-op).
Underlying congenital myopathies (e.g., Central Core Disease, King-Denborough syndrome).
III. Quick Pathophysiology
The triggering agent hits the defective RYR1 receptor on the sarcoplasmic reticulum. This leads to a massive, sustained flood of calcium into the muscle cell cytoplasm. This uncontrolled calcium causes:
Sustained Muscle Contraction: Leads to rigidity (e.g., masseter spasm) and muscle breakdown (rhabdomyolysis).
Hypermetabolism: The cell's mitochondria go into overdrive trying to pump the calcium back. This consumes huge amounts of oxygen and produces enormous amounts of CO2 (leading to hypercarbia) and heat (leading to hyperthermia).
Cell Lysis: Muscle cells break down, releasing potassium (hyperkalemia), myoglobin (myoglobinuria -> AKI), and creatine kinase (CK). The runaway metabolism also produces lactic acid, causing severe metabolic acidosis.
IV. Clinical Assessment
Red Flags & Immediate Actions (Intra-operatively):
Sudden, sharp rise in end-tidal CO2 (ETCO2): This is often the earliest and most reliable sign.
Action: Immediately rule out other causes (e.g., circuit hypoventilation), then assume MH. Alert the senior anaesthetist.
Masseter Muscle Rigidity (MMR): Jaw stiffness after giving succinylcholine.
Action: Stop the procedure if elective. Alert the senior. Monitor closely for other signs of MH.
Unexplained Tachycardia & Arrhythmias: Heart rate is climbing despite adequate anaesthetic depth.
Action: Alert the senior. Get an ABG to check for acidosis and hyperkalemia.
Rapidly Increasing Temperature: Hyperthermia is a LATE, and often pre-terminal, sign.
Action: If you see this, the crisis is already advanced. Initiate active cooling immediately.
History (Pre-operative Assessment):
The most important questions you can ask:
"Have you or anyone in your family ever had a problem with anaesthesia?"
"Any family history of muscle diseases or disorders?"
"Have you ever had a high fever or dark urine after an operation?"
Physical Examination (Intra-operative Signs):
Early: Tachycardia, tachypnea (if spontaneously breathing), rising ETCO2, muscle rigidity (especially the jaw), skin mottling, cyanosis.
Late: Hyperthermia (>38.8°C, rising rapidly), cardiac arrhythmias (often from hyperkalemia), cola-coloured urine (myoglobinuria), generalised muscle rigidity like a board.
Clinical Pearl: Don't wait for the fever. The thermometer is the last thing to tell you that you're in trouble. Your first clue will almost always be on the anaesthetic monitor's capnograph.
V. Diagnostic Workflow
This is a clinical diagnosis made in an emergency. You don't have time for complex investigations.
Differential Diagnosis:
Inadequate Anaesthesia/Analgesia:
Points For: Tachycardia, hypertension.
Points Against: No dramatic rise in ETCO2, no rigidity, symptoms resolve with deepening anaesthesia.
How to Differentiate: Give a bolus of opioid or propofol. If it resolves, it's not MH.
Sepsis:
Points For: Tachycardia, fever, acidosis.
Points Against: Onset is usually slower. ETCO2 rise is less dramatic. No muscle rigidity.
How to Differentiate: Clinical context. Is the patient septic pre-op? MH is an immediate intra-op event.
Thyroid Storm:
Points For: Tachycardia, hyperthermia, altered mental status.
Points Against: Usually a known history of thyrotoxicosis. No generalised rigidity.
How to Differentiate: History and absence of rigidity.
Investigations Plan (To be done concurrently with management):
Bedside / Initial:
Arterial Blood Gas (ABG): Crucial. Will show a classic picture of severe mixed respiratory and metabolic acidosis, high PaCO2, low pH, and often life-threatening hyperkalemia. Repeat this frequently to guide therapy.
ECG: Look for signs of hyperkalemia (peaked T waves, wide QRS).
First-Line Labs:
Creatine Kinase (CK): Will be massively elevated (>10,000 IU/L, often >100,000). Send it STAT, but don't wait for the result to treat.
Renal Profile & Electrolytes: To monitor potassium and for developing Acute Kidney Injury (AKI).
Urine for Myoglobin: Confirms rhabdomyolysis.
Coagulation Profile: To screen for Disseminated Intravascular Coagulation (DIC), a common complication.
Confirmatory / Gold Standard (Done electively, not in the acute setting):
Caffeine-Halothane Contracture Test (CHCT): Requires a fresh skeletal muscle biopsy. This is the gold standard for diagnosis. Patient is referred to a specialised centre (e.g., in HKL or UMMC) for this after they recover.
Genetic Testing: For RYR1 mutations.
VI. Staging & Severity Assessment
We use a clinical grading scale to quantify the likelihood of MH. The Larach et al. scale is standard. It assigns points based on clinical indicators:
Process indicators: Rigidity, muscle breakdown (CK > 20,000).
Metabolic indicators: Respiratory acidosis (ETCO2 > 55, PaCO2 > 60), metabolic acidosis (base excess more negative than -8).
Temperature indicators: Abnormally rapid temperature increase.
Cardiac indicators: Unexplained tachycardia, ventricular arrhythmias.
A raw score is calculated. This helps retrospectively confirm the diagnosis and guide counselling, but in the moment, high clinical suspicion is enough to trigger full treatment.
VII. Management Plan
This is a protocol. It should be on a chart in every operating theatre.
Immediate Stabilisation (The "SOMEBODY GET DANTROLENE" Plan):
Stop Triggering Agents: Immediately discontinue all volatile anaesthetics and succinylcholine. Announce the emergency to the room.
Call For Help: This is not a solo job. Call for the senior anaesthetist, other anaesthetic MOs, and OT staff. Designate one person to get the MH cart/trolley.
Hyperventilate: Increase the fresh gas flow to the maximum (10-15 L/min) with 100% oxygen to flush out the volatile agent and lower PaCO2. Change the breathing circuit and CO2 absorber if possible.
Administer DANTROLENE: This is the specific antidote.
Dose: 2.5 mg/kg IV initial bolus.
Preparation: Each vial contains 20mg and must be reconstituted with 60ml of sterile water (NOT saline). You will need many vials and many hands to do this quickly.
Repeat: Continue giving 1 mg/kg boluses every 5-10 minutes until the ETCO2, heart rate, and rigidity start to normalise.
Cool the Patient:
Stop all active warming.
Administer cold IV normal saline (4°C).
Apply ice packs to groin, axillae, and neck.
Use surface cooling blankets.
Treat Acidosis & Hyperkalemia:
Acidosis: IV Sodium Bicarbonate 1-2 mmol/kg, guided by ABG.
Hyperkalemia: IV Calcium Chloride (to stabilise myocardium), followed by IV Insulin/Dextrose.
Manage Arrhythmias: Standard ACLS protocols. Avoid calcium channel blockers as they can interact with dantrolene.
Maintain Urine Output: Give IV fluids and a diuretic like Furosemide or Mannitol to maintain UO > 1 ml/kg/hr and prevent myoglobinuric AKI.
Definitive Treatment (The ICU Plan):
The patient must be transferred to ICU post-stabilisation.
Continue IV Dantrolene at 1 mg/kg every 4-6 hours for at least 24-48 hours to prevent recurrence.
Continue intensive monitoring of core temperature, ABG, electrolytes, CK, and renal function.
Watch for complications like DIC, AKI, and compartment syndrome.
Long-Term & Discharge Plan:
Patient and family must receive genetic counselling.
Referral to a specialised MH diagnostic centre for contracture testing.
Provide a medical alert letter/bracelet stating they are MH-susceptible.
All first-degree relatives must be informed as they have a 50% chance of being susceptible.
VIII. Complications
Immediate (Minutes to Hours):
Cardiac Arrest: Management: Follow ACLS, aggressively treat hyperkalemia.
Acute Kidney Injury: Management: Force diuresis with fluids and diuretics. May require haemodialysis.
Disseminated Intravascular Coagulation (DIC): Management: Correct underlying cause, give FFP, cryoprecipitate, platelets.
Cerebral Edema: Management: Elevate head of bed, hyperventilate, consider mannitol.
Short-Term (Days):
Compartment Syndrome: Management: Regular limb checks, requires emergency fasciotomy if present.
Pulmonary Edema: Management: Diuretics, ventilatory support.
Long-Term (Weeks to Months):
Myalgia and muscle weakness: Management: Physiotherapy and supportive care.
IX. Prognosis
Without treatment, mortality is over 80%.
With prompt diagnosis and immediate administration of dantrolene, mortality is now less than 5%.
Key Prognostic Factors:
Early recognition (especially of rising ETCO2).
Speed of dantrolene administration.
Maximum core temperature reached.
X. How to Present to Your Senior
Use the SBAR format, but make it fast.
"Dr., I need you in OT 2 urgently for a suspected Malignant Hyperthermia.
Situation: Mr. Lim, a 30-year-old for an emergency appendicectomy.
Background: Induced with sevoflurane and suxamethonium 10 minutes ago.
Assessment: Post-intubation, his ETCO2 shot up from 35 to over 80. He is tachycardic at 150, and his jaw is rigid.
Recommendation: I have already stopped all volatile agents and am hyperventilating with 100% O2. I need you here now. The team is getting the MH cart and preparing dantrolene."
XI. Summary & Further Reading
Top 3 Takeaways:
Trust the Capnograph: A sudden, sustained rise in ETCO2 is your earliest, most reliable sign. Fever is late.
Dantrolene Saves Lives: Know the dose (2.5 mg/kg) and how to mix it. Don't delay.
It's a Team Sport: You cannot manage this alone. Call for help immediately.
Key Resources:
Malaysian Society of Anaesthesiologists (MSA): Check their website for local clinical practice guidelines on anaesthetic emergencies.
UpToDate: "Malignant hyperthermia: Diagnosis and management of acute crisis" - Excellent, evidence-based summary.
Amboss: "Malignant Hyperthermia" - Good for quick review and diagnostics.
